SummaryLangerin is a C‐type lectin receptor that is expressed on Langerhans cells and langerin‐positive dermal dendritic cells in the skin. Little is known about the function of langerin+ cells in wound healing. In this study, the effects of ablation of langerin+ cells on healing of a full‐thickness excision wound were investigated using the langerin‐DTR depletable mouse. Strikingly, depletion of langerin+ cells resulted in more rapid reduction in wound area. Accelerated wound healing in the langerin+‐cell‐depleted group was characterized by enhanced neo‐epidermis and granulation tissue formation, and increased cellular proliferation within the newly formed tissues. Accelerated healing in the absence of langerin+ cells was associated with increased levels of granulocyte–macrophage colony‐stimulating factor, F4/80+ cells and blood vessels within the granulation tissue. These data support an inhibitory role for langerin+ cells during wound healing. Therapies that suppress langerin+ cells or their function may therefore have utility in progressing the healing of wounds in humans.

Langerhans cells (LCs) are epidermal immune cells of myeloid origin. Although these cells were primarily thought to play a defensive role in the skin, evidence now indicates a diverse range of LC-mediated effects including the relay of viral antigens in herpes simplex infection, recruitment of eosinophils in atopic dermatitis and promotion of a Th17 response in Candida infection. LCs may have a protective or suppressive function in pathologies of the skin, with differing functions being driven by the skin milieu. Understanding LC function will help guide the development of interventions that modulate these cells for therapeutic benefit.

Accurate Rh testing can be difficult if the red cells are heavily coated with IgG anti D antibodies - a phenomenon called blocked D. Repeatedly, Rh D negative blood group report was obtained in a newborn male baby with severe haemolytic disease and features of kernicterus born to a 2nd gravida B Rh D negative mother. On investigation, the baby was grouped as B Rh D negative by direct grouping, but after elution, D antigen was detected and phenotyped as CcDe. Antibody was identified as anti D. All D antigens of the baby were fully saturated with anti D leaving any antigen to bind with antisera. Direct Coombs test was strongly positive even after three exchange transfusions. The baby also had free antibody apart from the red cell bound and the red cell eluate, gave a titre of 512. The mother was grouped as B Rh D negative and phenotyped as ce. She had IgM and IgG class of anti D with titres 32 and 1024 respectively. She also had IgM anti C (only in neat) and IgG anti-A with a titre of 512.

Background Progression of cervical intraepithelial neoplasia (CIN) to higher grade disease is associated with persistent human papillomavirus (HPV) infection and an absence of immune-mediated regression. However, the immune microenvironment that distinguishes progression from persistent or regressing lesions has not been well defined. Methods A total of 69 patients under the age of 25 with high-risk HPV-positive cytology and biopsy-confirmed p16-positive CIN2 were included in the study. Biopsies were stained using 20 antibodies to a range of immune markers. Based on a 2-year follow-up, samples were analysed in “progressor” (CIN3 +) or “persister/regressor” (CIN1, 2 or normal) groups. Results Progression was most strongly associated with Blimp-1 positive cell staining in the lesion (P = 0.0019) and with low numbers of infiltrating CD4 cells in the dermal region beneath the lesion (P = 0.0022). The presence of CD4, CD8 and T bet-positive cells in the dermal region most strongly correlated with CD11c cells in the persister/regressor but not the progressor group. Conclusion High numbers of Blimp-1 + cells in CIN2 lesions may predict progression to more severe disease. Measurement of Blimp-1 may have diagnostic utility for the determination of the need to treat women with cervical pre-cancer. Highlights CIN2 progression is associated with high numbers of Blimp-1 positive cells in the lesion. Detection of Blimp-1 in the lesion may have utility as a prognostic test to inform the need to treat CIN2.

Summary The role of antigen‐presenting cells in the skin immune system, in particular Langerhans cells and dendritic cells, has not been well defined. We recently published a study in ‘Immunology’ where we reported that the loss of langerin‐positive cells in the skin accelerated wound repair in the Lang‐DTR mouse. The study published here by Li, et al. reports delayed wound closure following depletion of CD11c‐positive cells in the CD11c‐DTR mouse. In this commentary, we attribute the differences between these results to several factors that differ between the studies including the depletion of different cell populations; differences in the age and the sex of mice; differences in antibiotic use between the studies; and differences in the location of the biopsies that were taken. Here, we describe the impact of these differences on wound healing and conclude that further standardization of the wound model, and further characterization of the specific cells that are depleted in these mice, is necessary to better understand how antigen‐presenting cells contribute to wound healing.

Cutaneous squamous cell carcinoma (cSCC) is a common cancer. Systemic immunosuppression with drugs such as Prednisone results in more aggressive disease. We hypothesise that more aggressive disease in immunosuppression is the result of immune changes in the tumor microenvironment. We characterised T cell, phagocytic and antigen presenting cell subsets in cSCC and determined if these infiltrates were altered by immunosuppressive therapy. We found a dominant “CD8 profile” in the centre of cSCC lesions, with CD8 cells correlating with Tbet, FoxP3, OX40 and “M2‐like” macrophages, whereas a “Tbet and granulocyte profile” with associated inflammation predominated at the margin of the tumor. Individuals on systemic immunosuppressive therapy had lesions that were comparable in size, stage and number of vessels to immune competent individuals; however, the number of CD11c positive cells in the lesion centre was significantly reduced. We conclude that cSCC lesions are immunologically heterogeneous across the lesion and that systemically immunosuppressed individuals have reduced CD11c positive cells in the centre of the lesion. The role and detailed phenotype of CD11c positive cells in cSCC lesions warrant further investigation.

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